当前位置： SCI文献检索 > AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY期刊下所有文献 > Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.

Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.

Abstract：

:Vascular endothelial growth factor (VEGF) is a potent peptide growth factor specific for vascular endothelial cells, which promotes neovascularization and increases vascular permeability in vivo. Enhanced microvascular permeability and edema are common characteristics of inflammatory and neoplastic disorders. Two proinflammatory mediators, platelet-activating factor (PAF) and platelet-derived growth factor (PDGF), are known to contribute to cellular damage and tissue remodeling in a number of lung diseases. To determine whether PAF or PDGF induce VEGF gene expression in primary cultures of human pulmonary fibroblasts and pulmonary vascular smooth-muscle cells (VSMCs), we performed Northern-blot analysis and enzyme-linked immunosorbent assays (EIA). PAF and all three isoforms of PDGF (PDGF-AA, -AB, and -BB) increased VEGF mRNA in a time- and dose-dependent manner. While PAF was shown to increase VEGF mRNA at picomolar concentrations, all PDGF isoforms were effective in inducing VEGF mRNA at nanomolar concentrations. The transcriptional activation was accompanied by increased levels of VEGF protein as determined by EIA in culture medium. These results indicate that VEGF gene expression in VSMCs and fibroblasts is mediated by PAF and/or PDGF isoforms. In a paracrine mode of action, secreted VEGF may then lead to altered endothelial cell functions and vascular hyperpermeability. In the presence of the corticosteroids cortisone, hydrocortisone, dexamethasone, or prednisolone at nanomolar concentrations, this stimulus-dependent transcription of VEGF was abolished. The inhibitory effect of corticosteroids on VEGF expression could explain the clinically well-known antiedematous potency of corticosteroids on a molecular level.

journal_name

Am J Respir Cell Mol Biol

journal_title

American journal of respiratory cell and molecular biology

authors

Nauck M,Roth M,Tamm M,Eickelberg O,Wieland H,Stulz P,Perruchoud AP

doi

10.1165/ajrcmb.16.4.9115750

subject

Has Abstract

pub_date

1997-04-01 00:00:00

pages

398-406

issue

eissn

1044-1549

issn

1535-4989

journal_volume

pub_type

杂志文章

在线工具

Induction of vascular endothelial growth factor by platelet-activating factor and platelet-derived growth factor is downregulated by corticosteroids.